Plastic collagen sutures



April 1, 1969 1 A. 'rl-lol-:NmsA

PLASTIC COLLAGEN SUTURES Filed nec. 1'?,` 1962 CHROM/C XDE INVENTOR.

Jaw/ence sfgoennes BY% Q United States Patent C) 3,435,825 PLASTICCOLLAGEN SUTURES Lawrence A. Thoennes, Chicago, Ill., assignor to TheKendall Company, Boston, Mass., a corporation of Massachusetts FiledDec. 17, 1962, Ser. No. 245,061 Int. Cl. A61] 17/00; D01f 5/00 U.S. Cl.12S-335.5 10 `Claims ABSTRACT OF THE DISCLOSURE This application isconcerned with plastic collagen sutures, specifically with chrome tannedsutures having the usual strength and body absorption propertiescharacteristic of chromicized sutures but unlike such sutures havingsufficient plasticity to permit easy removal of set bends therefrom bythe usual stretching procedure employed tby surgeons.

It is a characteristic of collagen sutures, tanned to increase strengthand body absorption time, to assume a permanent set when stored in theform of coils or in turns upon a reel in a confined package. Numeroussoftening agents including water and various plasticizers have beenapplied to such tanned collagen sutures in attempts to eliminate thistendency or at least to permit the easy removal of set bends when thesurgeon stretches the suture. However, all such softening agents orplasticizers when used in suflicient `amounts to be completely effectivehave seriously weakened collagen sutures so that tanned sutures as soldprior to this invention have been only partially plasticized. If oneobserves such tanned collagen sutures after stretching in the manneremployed by surgeons, the suture begins to retract as soon as thestretching force is removed and soon assumes an elongated form of theconfiguration it had when stored in the confinement of the suture tubeor package.

It is an object of this invention to provide tanned collagen suturescomparable in body absorption time and strength characteristics to usualchromicized `sutures but which, when stretched from a coil-likeconfiguration in the usual manner employed by surgeons, exhibit a verymuch reduced tendency to return to the original coiled form.

FIGURE l illustrates a coiled suture in a typical suture package.

FIGURE 2 illustrates a portion from a coil as in FIG- URE l of the usualChromed collagen suture after a 60- inch length has lbeen stretched witha 3-pound pull and allowed to relax for 5 minutes.

FIGURE 3 illustrates a portion from a coil as in FIG- URE 1 of acollagen suture of this invention after a 60- inch length has beenstretched with a 3-pound pull and allowed to relax for 5 minutes.

FIGURE 4 illustrates graphically the difference in elongation of coiledtanned collagen sutures of various chrome content, previously stored inwater and 90% ethanol, after such stretching.

The objects of this invention are obtained by treatment of raw collagenstrands with a combination of two compounds in solution preferably insuccession and preferably in a given order. Satisfactory results may beobtained, however, by treatment with the two compounds Patented Apr. 1,1969 combined and reacted into a single treating solution or bytreatment with the compounds successively in the reverse of thepreferred order.

In the preferred method of treatment, the raw collagen strand is firsttreated by immersion in a solution of a dichromate. Sodium dichromate isthe preferred dichromate ibut potassium dichromate, calcium dichromate,am monium dichromate or any other dichromate soluble to the extent of.01% in water at room temperature is suitable, it being necessary onlythat the dichromate ion be in suiiicient concentration in the water. ApH of 5 to 6V: is preferred. In tanning collagen strands according tothis method, the ratio of volume of solution to the weight of the strandhas little effect provided there is sufficient dichromate and reducingagent in solution. With concentrations of 0.1% sodium dichromate and0.2% pyrogallic acid, volume-weight ratios between 30-1 and 200-1 givevery little difference in the final chrome content of the suture or thedegree of plasticity produced when the time of immersion is maintainedconstant between 1 to 2 hours. With extremely dilute solutions of .01%or less, a longer period of immersion is necessary, being roughlyinversely proportional to the concentration of dichromate ions in thesolution. With a solution of .0025% dichromate, a l2-hour `bath followedby a 2-hour bath in .034% pyrogallic acid gave a chrome contentequivalent to that of an amount of chromic oxide .174% of the dryChromed suture weight.

After the proper period of immersion in the dichromate bath, thesolution is drained and replaced with a second bath of a solution of thephenol derivative defined below preferably having at least a mole tomole relationship with the dichromate in an equal volume bath. Thepreferred ratio of concentrations of the dichromate and phenolderivative solutions is when the first bath is a solution of sodiumdichromate and the second of equal volume is a solution of pyrogallicacid.

The phenol derivative is one or more of those selected from the groupconsisting of compounds corresponding to the formulae where R is ahydroxyl or an amino group and X is any radical chosen from the groupconsisting of hydrogen, hydroxyl, amino, an alkyl of less than 5 carbonatoms, carboxyl, nitro and carbalkoxyl radicals.

Afer immersion for from l to 3 hours -with 2 hours preferred in thephenol derivative bath in the preferred molar relationship, the collagenstrand will have been properly tanned and will be found to have a chromecontent equivalent to that of chromic oxide in the range of .1 to .3% ofthe dry chromed suture. The method of measuring the chrome content ofthe tanned collagen strand in terms of chromic oxide is as follows:

Ash .8 gram of dried Chromed collagen strand at 500 C. When cooled, boilthe ash in an Erlenrneyer fiask with 10 cc. of perchloric acid for 10minutes after the liquid turns orange. Cool and dilute to about 200 cc.with distilled water. Boil for 20 minutes, then cool to 65 F. Add 15-20cc. of concentrated hydrochloric acid and 10 cc. of potassium iodidesolution made by dissolving grams in 500 cc. of water. Titrate withstandardized sodium thiosulphate solution until the solution is paleyellow. Add

a few drops of starch indicator and titrate to the disappearance of anyblue coloration. Calculate cc. of Na2S2O3XFactorXl00 Wt. of sampleFactor is that obtained by multiplying the normality of Nagsgog Thepreferred chrome content of the tanned collagen strands of thisinvention is equivalent to that in an amount of chromic oxide in therange of .15% i.05% of the Weight of such strand. This is in distinctcontrast with the chrome content of chrome tanned collagen strands priorto this invention, the chrome content of which was normally equivalentto that of chromic oxide in amounts Percent Chromic Oxide:

4 tionship with the dichromate concentration. Where the bath volume incc. to the collagen weight in grams is in the range of 200 to 1, aphenol derivative concentration of .2% is preferred. With dichromateconcentrations in the range of .05% to .2%, a two-hour bath produceschromicized collagen sutures with chrome contents equivalent to that ofchromic oxide in the range of .17 to .2% of the dry chromicized suture.One may reduce the chrome content by reducing the bath period or one mayreduce the chrome content by retaining the two-hour bath period andreducing the dichromate concentration below .05% and down to about .03%to obtain sutures with chrome contents equivalent to chromic oxide inamounts as low as .1% of the dry weight of the chromicized suture.

about .5% and frequently in amounts as much as 2% of 15 One may alsoincrease the chrome content above the the dry Weight of the tannedcollagen strand. equivalent of .2% chromic oxide without modifying theIt has been discovered, however, that the proportion single bath byincreasing the period thereof so that at about of chrome equivalent tothat of chromic oxide above .3% 3 hours the chrome content will haveincreased to the of the dry tanned suture weight does not contributeapequivalent of about .3% chromic oxide. Sutures with preciably to itsstrength and may delay the rate of ab- Z chrome contents in the range of.2% to .3% equivalent sorption in the body undesirably. Such excessabove the chromic oxide are increasingly less plastic as the chromeequivalent amount of chrome in chromic oxide above .3% content increasesin this range, however until at .3% of the dry tanned gut does have avery adverse effect on chromic oxide equivalent, the plasticity isbarely satisfacthe plasticity of the tanned strand. At .3% chromic oxidetory. One-bath chromicization tends to produce sutures or below,equivalent chrome permits removal of configuwith the degree ofchromicization increasing from the cenrations by stretching to the pointwhere they are not parter of the suture outwardly whereas two-bathchromicizaticularly obvious or objectionable with the .3% equivalenttion gives a more uniform through and through chromichrome suture beingbarely satisfactory. With chrome concization. Moreover, the single-bathmethod tends to Ibe tents above this equivalent, the set configurationsbecome somewhat gummy so that a cleaning problem is involvedincreasingly more diicult to remove and constitute a most with regard tothe bath tanks. objectionable feature as can be easily observed. Whenthe preferred order of treatment is reversed with Examples of thetwo-bath method with the first bath the two-bath method so that thecollagen strand is first constituting the dichrornate solution are asfollows: treated with the phenolic derivative, the results are veryTABLE I Chrome 1st bath Concentra- Period (hr.) 2nd bath Concentra-Period (hr.) equiv. to

' tion, chromic percent percent oxide, percent Sodium dichromate 1 1Pyrogaliic acid 2 2 31 .1 1 do .2 2 .24 .1 1 .2 2 .24 .1 1 .2 2 .24 .1 1.2 2 .13 .1 1 .2 2 .17 .1 1 .2 2 .21 .1 1 in .2 2 .23 1 1Orthprotocatechuic 2 2 .14

acl 1 1 Orthoveratrlc acid 2 2 17 1 1 Amino phenol 2 2 16 1 1 Chestnutextract. 2 2 21 1 y Pyrogallic acid 2 2 03 .1 d .2 2 .21 .1 1 .2 .29.025 2 .2 2 .13 .025 1 .2 2 .1 .02 4 .2 2 .3 .01 4 .2 2 .1 .1 1 .1 4 .4.o5 1 .3 1 .17 .05 1 .1 4 .16 .o5 1 .2 2 .13 .05 1 .2 2 .11 05 1Hydroquinone 2 2 14 The accompanying graph FIGURE 4 illustrates averageincrease in length in inches 1 minute after momentarily stretching witha 3-pound pull, 60-inch pieces of collagen suture of various chromecontent stored in the form of circular coils of 11/2 inches in diameterfor a minimum period of 1 Week in tubing fluid of 10% water and 90%ethanol.

When the one-bath method of chromicization is utilized in accordancewith the invention, the phenol derivative concentration is preferably inexcess of the molar relacomparable with the results obtained when thestrand is first treated with the dichromate but it takes less dichromateto accomplish the same results. That is, where the period andconcentration of each bath is unchanged but the order is reversed, theprocedure in which the phenolic derivative bath is first, producessutures with higher chrome content. For that reason it is preferred touse the dichromate bath first since any error is less significant.

Typical of two-bath methods involving a phenolic derivative first bathare the following:

TABLE II Concentra- Concentra- Chrome 1st bath 'on, Period (hr.) 2ndbath tion, Period (hr.) equiv. to

percent percent chromic oxide, percent Pyrogallic acid 2 2 05 1 32 Do 22 025 1 21 Do 2 2 01 1 09 The particular tubing fluid used in storingcollagen sutures of this invention has considerable effect upon theplasticization of the suture. Water is normally considered a goodplasticizer for collagen sutures but both ethyl and methyl alcohol inthat order are superior plasticizers for such sutures when plasticity ismeasured by plastic elongation. Thus sutures chromicized in accordancewith this invention may be obtained in more plastic condition withhigher percentages of ethyl or methyl alcohol combined with lowerpercentages o'f water than are usual in 0 tubing fluids. A tubing Huidmade up of a solution of 98% ethyl alcohol and 2% water to which isadded .3% of ethylene oxide as a sterilizing agent is preferred. Thesutures of this invention in the preferred range of chrome contentequivalent to that in chromic oxide in the range of .1% to .2% of thedry weight of the suture are more plastic than plain untanned ornon-chromicized sutures. Thus in the tubing solution of FIGURE 4 whichwas 90% ethyl alcohol, 10% water to which was added .3% ethylene oxide,60-inch plain sutures averaged 1 inch increase in length when stretchedfor a minute with a 3-pound pull whereas sutures with chrome contentequivalent to .1 to .2% of the dry weight of the suture stretched more.As a more dramatic:` illustration of the superiority of chromicizedsutures of this invention over plain sutures in the matter of plasticityan experiment was performed using ive 10-foot strands of #1 catgut. Thestrands were cut in half and half of each strand was left untreated orplain and packaged in 2. cc. of preferred tubing solution. The otherhalf of each strand was treated with a solution of .04% sodiumdichromate for one hour after which the solution was drained andreplaced by a solution of .034% pyrogallic acid solution for two hourswhich was also drained. These treated sutures were later determined tohave a chrome content equal to that in chromic oxide in the amount of.17% of the dry weight of the suture. These suture halves of the 10-footoriginal strands were then packaged in 2 cc. of the same tubing iiuid asthe plain halves. After one week the packages were opened and thesutures were tested for plasticity by stretching the G10-inch lengthsfor l minute with a -pound pull and measuring the increase of lengthafter release. The plain suture halves had an increase in length of 1.15inches whereas the suture halves treated in accordance with thisinvention had an increase of 2.16 inches. With 45 sutures of greaterchrome content, the eiect of tubing uid is less pronounced. A suturehaving a chrome content equivalent to that of chromic oxide in an amount.3% of the dry weight of the suture was elongated .9 inch under the testconditions when tubed in 90% ethyl alcohol and 10% water to which .3%ethylene oxide was added as in FIGURE 4. When a similar suture was tubedin the preferred solution, its elongation under the same conditions was1.3 inches.

No. 1 sutures prepared by the usual chromicizing meth- 55 ods and havingan average chrome content equivalent to that in chromic oxide in amountof 1% of the dry suture weight were compared with No. l sutures preparedin accordance with this invention and having an average chrome contentequivalent to that in chromic oxide in amount of .17% of the dry sutureweight as follows:

TABLE III Chrome equiv. Straight pull Straight pull Knot strength tochromic oxide, dry (pounds) wet (pounds) (pounds) percent Straight pullafter indicated days in animal tissue (pounds) 0 days 7 days 14 days 21days 28days 42 days 70 Chrome equiv. to chromic oxide, percent I claim:

1. An absorbable chromicized raw collagen suture 75 comprising thereaction product of a raw natural collagen strand of the size and shapeof a suture, a dichromate salt having a solubility in water of at least0.01% at F. and a phenol derivative selected from the group consistingof compounds corresponding to the formulae wherein R is a memberselected from the group consisting of hydroxyl and amino, and X is amember selected from the group consisting of hydrogen, hydroxyl, amino,nitro, carboxyl, carbalkoxyl and loweralkyl having 1 to 5 carbon atoms,such that said reaction product has a chrome content equivalent to thatin chromic oxide weighing in the range of 0.1% to 0.3% of the dry weightof the suture.

2. An absorbable chromicized raw collagen suture according to claim 1wherein the dichromate salt is a member selected from the groupconsisting of sodium dichromate, potassium dichromate, calciumdichromate and ammonium dichromate.

3. An absorbable chromicized raw collagen suture according to claim 1wherein the chrome content of the reaction product is equivalent to thatin chromic oxide in the range of 0.1% to 0.2% of the `dry weight of thesuture.

4. An absorbable chromicized fraw collagen suture according to claim 1wherein the phenol derivative consists of pyrogallic acid.

5. A method of producing an absorbable chromicized raw collagen suturecomprising the steps of reacting a strand of ra-w natural collagen witha dichromate salt having a solubility in water of at least .01% at 70 F.and a phenol `derivative selected from the group consisting of compoundscorresponding to the formulae X X X R and X X X X wherein R is a memberselected from the group consisting of hydroxyl and amino, and X is amember selected from the group consisting of hydrogen, hydroxyl, amino,nitro, carboxyl, carbalkoxyl and loweralkyl having 1 to 5 carbon atoms,such that the reaction product has a chrome content equivalent to thatin chromic oxide weighing in the range of 0.1% to 0.3% of the dry weightof the suture.

6. A method in accordance with claim 5 wherein the raw natnural collagenis -rst treated with the dichromate salt followed by treatment with thephenol derivative.

7. A method in accordance with claiml 5 wherein the raw natural collagenis rst treated with the phenol derivative followed by treatment with thedichromate salt.

8. A method in accordance with claim 5 wherein the raw natural collagenis treated with a solution of the reaction product of the dichromatesalt and the phenol derivative.

9. A method in accordance with claim 5 wherein the dichromate salt is amem-ber selected from the group consisting ofsodium dichromate,potassium dichromate, calcium dichromate and ammonium dichromate.

10. A method in accordance with claim 5 wherein the dichromate saltconsists of sodium dichromate and the phenol derivative consists ofpyrogallic acid.

(References on following page) 7 8 References Cited by British Leather.Manu. Rec. Assoc., London, England,

T5965 B75. UNITED STATES PATENTS Gustavson: The Chemistry and Reactivityof Colla- 542,971 7/1895 Amend 8 9426 gen, pages 171, 172, 192-196, Pub.1956 by Academic 987,750 3/1911 Seyewitz et a1 8 94.33 5 Press, 111C-,QD 431G8 2,519,404 8/195() Rynkiewicz 12g 335 5 Shuttleworth: J. Int.S-oc. Lea. Trades Chem., pages 2,576,576 11/1951 Cressweu et a1.12s-335.5 281-282 8/94-27- 2,640,752 6/1953 Davis 8 9411 Wllson: TheChemlstry of Leather Manufacture, pages 3,093,439 6/1963 Borhweu 8 94,11649-650, 690-696, Pub. 1929, vol. II, by The Chem. 2,475,697 7/1949Cresswen 264-202 10 Catalog Company, Im, N.Y.C., T5965 W5 1928.

OTHER REFERENCES DONALD LEVY, Primary Examiner.

Dempsey: Progress in Leather Science, Chapter One, l US- C1. X-R- TheHistory of Hides and Skins, pages 3-7, Pub. 1948, g 94 11 UNITED STATESPATENT OFFICE CERTIFICATE 0F CORRECTION Patent No. 3,435,825

April 1, 1969 Lawrence A. Thoennes It is certified that error appears inthe above identified stent and that said Letters Patent are herebycorrected as P shown below:

Column 6, line l, before "a" insert applying to line 59, natnural shouldread natural Signed and sealed this 14th day of April 1970.

(SEAL) Attest:

WILLIAM E. SCHUYLER, JR.

Edward M. Fletcher, Jr.

Commissioner of Patents Attesting Officer

